The Relationship between Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease Measured by Controlled Attenuation Parameter

PURPOSE: The severity of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) population compared with that in normal glucose tolerance (NGT) individuals has not yet been quantitatively assessed. We investigated the prevalence and the severity of NAFLD in a T2DM population using controlled attenuation parameter (CAP). MATERIALS AND METHODS: Subjects who underwent testing for biomarkers related to T2DM and CAP using Fibroscan® during a regular health check-up were enrolled. CAP values of 250 dB/m and 300 dB/m were selected as the cutoffs for the presence of NAFLD and for moderate to severe NAFLD, respectively. Biomarkers related to T2DM included fasting glucose/insulin, fasting C-peptide, hemoglobin A1c (HbA1c), glycoalbumin, and homeostasis model assessment of insulin resistance of insulin resistance (HOMA-IR). RESULTS: Among 340 study participants (T2DM, n=66; pre-diabetes, n=202; NGT, n=72), the proportion of subjects with NAFLD increased according to the glucose tolerance status (31.9% in NGT; 47.0% in pre-diabetes; 57.6% in T2DM). The median CAP value was significantly higher in subjects with T2DM (265 dB/m) than in those with pre-diabetes (245 dB/m) or NGT (231 dB/m) (all p<0.05). Logistic regression analysis showed that subjects with moderate to severe NAFLD had a 2.8-fold (odds ratio) higher risk of having T2DM than those without NAFLD (p=0.02; 95% confidence interval, 1.21-6.64), and positive correlations between the CAP value and HOMA-IR (ρ=0.407) or fasting C-peptide (ρ=0.402) were demonstrated. CONCLUSION: Subjects with T2DM had a higher prevalence of severe NAFLD than those with NGT. Increased hepatic steatosis was significantly associated with the presence of T2DM, and insulin resistance induced by hepatic fat may be an important mechanistic connection.

[Effects of total extract of urtica dioica on insulin and c-peptide secretion from rat [RIN5F] pancreatic beta cells and glucose utilization by human muscle cells]

The hypoglycemic effects of the Uritca Dioica [UD] extract, used for treatment of diabetes mellitus for many centuries, have been documented in several studies. The present study was designed to determine the possible mechanisms of hypoglycemic effects of UD on human muscle cells and RIN5F rat pancreatic beta cells. In the cell culture laboratory of the Drug Applied Research Center, pancreatic Beta cells and human muscle cells were prepared in multiple flasks containing culture media. Alcoholic extract of UD at concentrations of 50, 100 and 200 micro g/mL were added to muscle cell flasks. The same concentrations of extract plus insulin were added to other muscle cell flasks.Glucose levels were measured in the flasks before and after 60, 120, and 180 minutes after adding of extract. Also the same concentration of UD were added to flask containing RIN5F rat pancreatic beta cells, and insulin and C-peptide level were measured at 0, 60, 120 and 180 minutes. Mean glucose level in the muscle cell media with UD alone and UD plus insulin, at the concentrations and time intervals mentioned, did not change significantly. Insulin levels in pancreatic cells media, before and after applying of UD at different concentrations, and at different times was

Avaliação da função pancreática em pacientes com diabetes melito tipo 1 de acordo com a duração da doença / Pancreatic function assessment in type 1 diabetes mellitus patients according to disease duration

Os pacientes com diabetes melito tipo 1 (DM1) podem apresentar secreção residual de insulina por longos períodos, o que tem sido associado a prognóstico mais favorável. OBJETIVO: Avaliar a secreção de insulina por meio da dosagem de peptídeo C (PC) em pacientes com DM1 de curta (<5 anos; grupo 1) e longa (> 5 anos; grupo 2) duração da doença. PACIENTES E MÉTODOS: Voluntários com DM1 coletaram sangue em jejum e 6 minutos após a infusão de glucagon para dosagem de PC, HbA1c e anti-GAD. RESULTADOS: Foram avaliados 43 pacientes, 22 no grupo 1 e 21 no grupo 2. Secreção de insulina preservada (PC > 1,5 ng/mL) foi identificada em seis (13,9 por cento) e oito (18,6 por cento) casos nas coletas basal (PC1) e após estímulo (PC2), sem diferença entre os grupos (p = 0,18 e 0,24). PC1 foi detectável (> 0,5 ng/mL) em 13 (30,2 por cento) e PC2 em 18 (41,9 por cento) casos, mais frequentes no grupo 1 do que no 2 (p = 0,045 para PC1/p = 0,001 para PC2). Os títulos de PC1 (1,4 ±0,8 versus 1,2 ±1,0; p = 0,69) ou PC2 (1,8 ±1,5 versus 1,7 ±0,8; p = 0,91) não diferiram entre os grupos. No grupo 1 houve correlação inversa entre tempo de doença e PC2 (R = -0,58; p = 0,025). CONCLUSÃO: Uma proporção significativa dos pacientes com DM1 apresenta secreção residual de insulina, especialmente nos primeiros cinco anos da doença. Tais indivíduos representam a população ideal para estudos visando à prevenção secundária da doença.

Patients with type 1 diabetes (T1D) may exhibit some residual insulin secretion for many years after their diagnosis. This has been associated with a more favorable prognosis. OBJECTIVE: To analyze insulin secretion in individuals with T1D using C-peptide (CP) response to glucagon and comparing patients with recent onset (<5 years - Group 1) and long-standing disease (>5 years -Group 2). METHODS: Subjects with T1D had their blood sampled before (fasting) and 6 minutes after glucagon infusion for CP, HbA1c and anti-GAD measurement. RESULTS: Forty-three individuals were evaluated, 22 in Group 1 and 21 in Group 2. Preserved insulin secretion (CP >1.5 ng/mL) was observed in 6 (13.9 percent) and in 8 (18.6 percent) patients before (CP 1) and after (CP 2) glucagon stimulus, respectively, showing no difference between the groups (p=0.18 and 0.24). CP 1 and CP 2 were detectable (>0.5 ng/dL) in 13 (30.2 percent) and 18 (41.9 percent) patients, respectively. Both were more frequent in Group 1 than in Group 2 (p=0.45 for CP1/p=0.001 for CP 2). Similar serum levels where seen between the groups, both before and after stimulus (1.4±0.8 vs. 1.2±1.0; p=0.69 and 1.8±1.5 vs. 1.7±0.8; p=0.91). Group 1 presented an inverse correlation between disease duration and CP 2 (R=-0.58; p=0.025). CONCLUSION: A significant number of patients with T1D have detectable residual insulin secretion, especially in the first 5 years of disease. These subjects are an ideal population for clinical trials that target the prevention of â cell function loss in T1D.

Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabettes and in Arab control subjects. Ninety-two patients [65 females and 27 males] with type 2 diabetes and 69 matched normal control subjects [48 females and 21 males] were included. Anthropometric measures [including body mass index [BMI] and waist:hip ratio] were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters including glucose, insulin, C-peptide, intact proinsulin, insulin resistance index [HOMA-IR], insulin-like growth factor 1 [IGF-1], lipids and hemoglobin A1c [HbA[1C][C]] were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein [HDL] cholesterol were similar in pattients with type 2 diabetes and control subjects. When obese subjects [BMI >/= 30 kg/m[2]] were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA[1C], and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BMI, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low

Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 + or - 8.3 years, with a duration of diabetes of 10.6 + or - 6.6 years, fasting plasma glucose of 277.3 + or - 64.6 mg/dl and a body mass index of 27.4 + or - 4.8 kg/m². Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedtime NPH insulin (phase 2), and insulin (phase 3). At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01). Twelve patients (48 percent) reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8) vs 66.7 kg (42.8-101.4) (P<0.05), with no increase in C-peptide secretion or decrease in HbA1. C-Peptide glucose score (C-peptide/glucose x 100) increased from 0.9 (0.2-2.1) to 1.3 (0.2-4.7) during combined therapy (P<0.01). Despite a 50 percent increase in insulin doses in phase 3 (12 U (9-30) vs 18 U (11-60); P<0.01) only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02). A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5) vs 0.6 (0-2.15); P = 0.08) and C-peptide incremental area (2.47 (0.22-6.2) vs 1.2 (0-3.35); P = 0.07) was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response

Permanent neonatal diabetes mellitus: epidemiology, mode of presentation, pathogenesis and growth.

Permanent neonatal diabetes mellitus (PNIDDM) is a rare form of IDDM with unclear etiology and pathogenesis. We determined the incidence and prevalence rates and studied the clinical and biochemical features of PNIDDM in the Sultanate of Oman. The mean incidence rate during the study period from January 1989 to December 1994 was 1.788 +/- 0.82 per 100,000 live births per year. At the end of December 1994 the prevalence rate was 2.4 per 100,000 children below the age of 5 years. They constituted 41.6% of all cases of IDDM in this age group. Diarrhoea, fever, lethargy, poor feeding and failure to thrive were the most common presenting symptoms. Dehydration and tachypnoea were the most common signs. All patients who developed IDDM during the neonatal period had intrauterine growth retardation and 4.5 presented with diabetic ketoacidosis (plasma glucose 37 +/- 9 mmol/L, pH 7.12 +/- 0.1). Hypertriglyceridemia was a constant feature (19.4 +/- 4.8 mmol/L). They were products of consanguineous marriage with significantly high prevalence of IDDM and NIDDM in their family members. None of the infants had clinical or immunological evidence of congenital viral infection. Three of the five children had HLA-DR2, the diabetes resistance alleles. C-peptide secretion was absent during and after metabolic control of hyperglycemia in all the studied infants and none had circulating islet cell antibody at presentation or during the first year after diagnosis. Despite marked growth retardation at birth, there was a significant improvement of growth after initiating insulin therapy. Four of the 5 patients had normal developmental milestones, one had mild developmental delay following a severe and prolonged attack of hypoglycemia. None of the patients had exocrine pancreatic deficiency. In summary, the very high rate of parental consanguinity, occurrence in both sexes and in two siblings in the same family, absence of islet cell antibodies and the presence of HLA-DR2 loci in 3/5 of patients suggest that PNIDDM is a different disease process to standard IDDM in childhood and an autosomal recessive mode of transmission.

Correlaçäo entre a resposta de peptídeo-C a uma refeiçäo padräo e diferentes parâmetros clínicos, bioquímicos e epidemiológicos do diabetes mellitus do tipo I / Correlation between C-peptide response to a pattern meal and different clinic, biochemical and epidemiologic parameters of diabetes mellitus type I

Com o objetivo de estudar a correlaçäo entre a funçäo residual da célula beta (e parâmetros clínicos, bioquímicos e epidemiológicos do diabetes, empreendemos um estudo de corte transverso, em 26 diabéticos insulino dependentes (12 do sexo feminino) com idades de 10 a 40 anos (21,1+8,2) e duraçäo da doença de 1 a 24 meses (7,9+6,7). O estímulo empregado foi uma refeiçäo padräo mista e as variáveis do peptídeo-C estudadas foram: peptídeo-C basal (PB), valor de pico (VP), área incremental (AI). Näo observamos correlaçäo entre as variáveis da curva de resposta do peptídeo-C e os seguintes parâmetros: idade de eclosäo da doença, duraçäo dos sintomas antes do diagnóstico, duraçäo do diabetes e níveis de glicemia basal, näo havendo também diferença entre os sexos. Observamos correlaçäo inversa e significativa entre a dose de insulina diária e a AI (rS= -0,44; p<0,04), e entre os níveis de hemoglobina glicolisada e o PB (rS = -0,41; p<0,05). Os pacientes com níveis de hemoglobina glicosilada = 9,5 por cento apresentavam valores mais elevados de PB (p<0,02), e aqueles que eclodiram a doença em cetoacidose apresentavam todas as variáveis da curva significativamente reduzidas (p<0,04). Concluímos que, no grupo estudado, a melhor capacidade de incremento pós-estímuo estava associada ao uso de menores doses de insulina, e que melhores níveis de hemoglobina glicolisada estavam associados a maiores níveis basais de peptídeo-C. A presença de cetoacidose no diagnóstico foi associada a um pior padräo de secreçao residual da célula beta nos dois primeiros anos de doença.

Hyper insulinism and decreased insulin sensitivity in nonobese healthy offspring of conjugal diabetic parents and individuals with IGT and NIDDM.

Insulin sensitivity was measured by insulin tolerance test using KITT as an index of insulin mediated glucose metabolism in 9 non-obese healthy offspring of conjugal diabetic parents (OCDP) and 9 non-obese NIDDM patients. The mean KITT value in the offspring of conjugal diabetic parents was 3.85 +/- 1.64 min-1 x 100 which was lower (P < 0.05) than the value of 5.49 +/- 1.9 min-1 x 100 in the control subjects. While, the mean KITT value in NIDDM patients was 1.85 +/- 0.9 min-1 x 100 which was significantly lower (P < 0.001) than that in the control subjects. Estimation of plasma immunoreactive insulin (IRI) and C-peptide in these subjects and in subjects with impaired glucose tolerance (IGT) showed significantly higher levels of insulin than that in the control subjects but there was no corresponding increase in the C-peptide levels. The mean area under the insulin curve (IRI) was 242 +/- 69 microU/ml in the control subjects versus 527 +/- 206 microU/ml in IGT (P < 0.001), 648 +/- 215 microU/ml in NIDDM (P < 0.001) and 466 +/- 130 microU/ml in OCDP (P < 0.001). These results suggest that 1) healthy offspring of two type II diabetic parents have decreased insulin sensitivity and insulin resistance is present in all the NIDDM patients, 2) peripheral hyperinsulinism is a common feature in healthy offspring of conjugal diabetic parents, and in subjects with IGT and mild NIDDM and this hyperinsulinism is not due to increased B-Cell secretion but due to some metabolic alterations of insulin occurring at the extra pancreatic levels.

Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus.

Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.

C-peptide profiles in young diabetics.

Fifty-six patients who had been diagnosed diabetic prior to the age of 30 were evaluated to determine the C-peptide (CP) secretory response to a glucose load. These individuals were classified clinically as having insulin dependent (IDDM = 18); non-insulin dependent (NIDDM = 19) and insulin requiring diabetes (IRDM = 19). Insulin dependent diabetics had lower basal CP levels (0.44 +/- (SE) 0.1 ng/ml) which were not stimulated by hyperglycaemia (0.55 +/- 0.13 ng/ml) as compared to controls (basal CP = 1.6 +/- 0.2 and peak 6.2 +/- 0.8 ng/ml). Non-insulin dependent diabetics and insulin requiring diabetics could be divided broadly into two groups - one, a set of patients with low basal CP levels (NIDDM = 0.63 +/- 0.09 ng/ml) (IRDM = 0.38 +/- 0.08 ng/ml) and a blunted response to a glucose load (peak response NIDDM = 0.83 +/- 0.05 ng/ml, IRDM = 0.59 +/- 0.12 ng/ml) and a second group who had CP reserve evident in both fasting (NIDDM = 1.6 +/- 0.2 ng/ml; IRDM = 2.1 +/- 0.6) and post-glucose levels (Peak Response NIDDM = 4.6 +/- 0.4 ng/ml; IRDM = 3.0 +/- 0.6 ng/ml). Growth Hormone (GH) and cortisol levels were found to be high in patients with IDDM and IRDM with no insulin reserve and these did not suppress during the oral Glucose Tolerance Test. NIDDM patients with no insulin reserve had normal GH and high cortisol levels. It is emphasized from this study that insulin sensitivity is as important as the insulin secretory status in determining the presenting features of diabetes mellitus in the young.